In the United States prostate cancer is first in absolute incidence with an estimated 210,000 new cases in 1997, and second to lung cancer for deaths with an estimated 41,800 deaths in 1997. Parker et al., 1997, Cancer Abstracts 47(1):5-27. The incidence of prostate cancer has risen at an average annual rate of 3% per annum from 1960 to 1985. Boyle, 1997, Proceedings--First International Consultation on Prostate Cancer. Prostate cancer affects older men with the rates of incidence for men in their 40's being 1-2 per 100,000, the rates for Caucasian men in their 80's 1,200 per 100,000 and for African American men 1,600 per 100,000. In 1900 only 25% of the United States population lived to the age of 65. Currently that number is 70%. Brody, 1985, Nature 315:463-466.
The guidelines for diagnosis of new prostate cancer adopted by the American Cancer Society in June 1997 recommends an annual prostate specific antigen (PSA) exam as well as a digital rectal exam (DRE) for men over 50 years of age and in certain instances over the age of 45. Further action should be taken only if one or both screening methodologies are abnormal. An abnormal PSA is defined as a PSA greater than 4.0 ng/ml.
Patients suspected of having prostate cancer based on a PSA test and a DRE, would then undergo additional radiographic and/or surgical tests to confirm diagnosis. These additional tests may include urology consultation, ultrasound and tissue biopsy with pathological evaluation. The cost associated with these confirmatory tests typically exceeds $5000.
The PSA test and DRE are acceptable screening methods but one of the short comings of these screening methods is the large number of falsely identified patients. A PSA European screening study biopsied 976 men and detected 190 cases of prostate cancer. 767 of the 976 men had either of both a PSA value in the range of 4 to 10 ng/ml or a suspect DRE. Of these 767 patients, only 177 had prostate cancer. 77% of the population did not have prostate cancer. Schroder, 1997, First International Consultation on Prostate Cancer, 179-210.
Final determination of prostate cancer must be made with more expensive and invasive biopsy. However, even a single biopsy can miss prostate cancer. In one third of patients who underwent a serial biopsy study, multiple biopsies were required for the detection of prostate cancer. Keetch et al., 1994, J. Urol. 151:1571-1574.
A recent methodology attempted to further identify patients who are at risk for prostate cancer has been the determination of percent free PSA. Murphy et al., 1996, Cancer 78(4):809-818, report a difference in the ratio of free PSA to total PSA in 226 patients with benign prostatic hyperplasia and patients with no evidence of disease compared to the same ratio in patients with biopsy-proven prostate cancer. The ratio was 12.1% in patients with no evidence of prostate cancer and in the prostate cancer group the ratio was 7.1%. Despite the differences observed, the authors concluded that their data suggest that free PSA values do not provide additional diagnostic benefit compared to total PSA in screening populations in the presence of suspected cancer, post prostatectomy or in metastatic disease. Pronounced differences in the ability of available assays to detect free PSA have generated multiple cutoffs, ranging from 15-20%. Catalona et al., 1996, JAMA 274:1214-1220; Oesterling et al., 1995, J. Urol. 154:1090-1095; Toubert et al., 1996, Eur. J. Cancer 32A(12):2088-2093; Lilja, 1993, Urol. Clin. North Am. 20(4):681-686. Regardless of the potential sensitivity gained, prostate cancer will have to be confirmed with a cytological assessment. Clearly, the development of a non-invasive, cytologically based assay, able to compliment the traditional PSA and DRE, would assist the clinician in the early detection and treatment of prostate cancer without the necessity of relying on more expensive invasive means.
Citation or identification of any reference in Section 2 or any other section of this application shall not be construed as an admission that such reference is available as prior art to the present invention.